title: Macrophage scavenger receptor 1 (Msr1, SR-A) influences B cell autoimmunity by regulating soluble autoantigen concentration.
abstract: The class A macrophage scavenger receptor Msr1 (SR-A, CD204) has been reported to participate in the maintenance of immunological tolerance. We investigated the role of Msr1 in a mouse model of autoantibody-dependent arthritis. Genetic deficiency of Msr1 in K/BxN TCR transgenic mice decreased the incidence and severity of arthritis because of decreased autoantibody production. Despite normal initial activation of autoreactive CD4(+) T cells, potentially autoreactive B cells in Msr1(-/-) K/BxN mice retained a naive phenotype and did not expand. This was not due to an intrinsic B cell defect. Rather, we found that macrophages lacking Msr1 were inefficient at taking up the key autoantigen glucose-6-phosphate isomerase and that Msr1-deficient mice had elevated serum concentrations of glucose-6-phosphate isomerase. Arthritis developed normally when bone marrow from Msr1(-/-) K/BxN mice was transplanted into hosts whose macrophages did express Msr1. Thus, Msr1 can regulate the concentration of a soluble autoantigen. In this model, the absence of Msr1 led to higher levels of soluble autoantigen and protected mice from developing pathogenic autoantibodies, likely because of altered cognate interactions of autoreactive T and B cells with impaired differentiation of follicular Th cells.
authors.affiliation: Department of Pediatrics, Center for Immunology, University of Minnesota, Minneapolis, MN 55414, USA.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Haasken
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Auger
authors.forename: Justin J
authors.initials: JJ
authors.lastname: Taylor
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Hobday
authors.forename: Brian D
authors.initials: BD
authors.lastname: Goudy
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Titcombe
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Mueller
authors.forename: Bryce A
authors.initials: BA
authors.lastname: Binstadt
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology* / Q000378:metabolism; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005956:Glucose-6-Phosphate Isomerase / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; C495140:Msr1 protein, mouse; D051117:Scavenger Receptors, Class A; D005956:Glucose-6-Phosphate Isomerase